Activity has been identified as an important factor in the development of normal patterns of connectivity and responsivity in the neocortex. Specific patterns of input, or "use", appear to activate the cortex in a manner that leads to the most efficient responses and patterns of neural connectivity. The responses and connections can change according to the level of input, or activity. Such use-dependent plastic changes are especially evident in developing animals, but occur in adults as well. Mechanisms suggested to mediate such neuronal plasticity include the observations that (i) receptors selective to a specific excitatory amino acid (N-methyl-D-aspartate; NMDA) are more effective during increased depolarization and (ii) acetylcholine increases response selectivity int he neocortex. The nucleus basalis is the primary source of acetylcholine in the neocortex. The hypotheses proposed here are (i) that neuronal plasticity can be clearly demonstrated in the somatosensory cortex of adult cats and kittens and (ii) that similar mechanisms operate in adults and neonates to produce such plastic changes. The first phase of research will study the normal developmental pattern of activity in the somatosensory cortex of kittens. The patterns will be assessed using the 2-deoxyglucose technique for metabolic mapping; a controlled mechanical stimulus will be delivered during 2DG administration. The relation of the stimulus-evoked patterns to connections within and to the cortex will be studied using injections of WGA-HRP into electrophysiologically defined sties of the thalamus and somatosensory cortex. Second, the effect of changing the input to the somatosensory cortex will be assessed by amputating a single digit and observing its chronic impact on (a) the evoked metabolic pattern in the somatosensory cortex of cat and kittens and (b) the relationship between the stimulus-evoked activity pattern and the connections to and within the somatosensory cortex. Third, the chronic effect of specific substance known to alter activity levels in sensory cortex will be analyzed in cats and kittens following amputations. This will be accomplished by (i) chronic treatment with an NMDA antagonist immediately following digit amputation and (ii) lesions of the nucleus basalis that deplete the neocortex of acetylcholine, also coupled with digit amputation. I propose that plastic changes will be more evident when digit amputations are carried out in kittens, but that plastic changes can be impeded in kittens and adults by cholinergic deprivation or by blockade of NMDA receptors.